Genes, mutations, and human inherited disease at the dawn of the age of personalized genomics

Hum Mutat. 2010 Jun;31(6):631-55. doi: 10.1002/humu.21260.


The number of reported germline mutations in human nuclear genes, either underlying or associated with inherited disease, has now exceeded 100,000 in more than 3,700 different genes. The availability of these data has both revolutionized the study of the morbid anatomy of the human genome and facilitated "personalized genomics." With approximately 300 new "inherited disease genes" (and approximately 10,000 new mutations) being identified annually, it is pertinent to ask how many "inherited disease genes" there are in the human genome, how many mutations reside within them, and where such lesions are likely to be located? To address these questions, it is necessary not only to reconsider how we define human genes but also to explore notions of gene "essentiality" and "dispensability."Answers to these questions are now emerging from recent novel insights into genome structure and function and through complete genome sequence information derived from multiple individual human genomes. However, a change in focus toward screening functional genomic elements as opposed to genes sensu stricto will be required if we are to capitalize fully on recent technical and conceptual advances and identify new types of disease-associated mutation within noncoding regions remote from the genes whose function they disrupt.

Publication types

  • Review

MeSH terms

  • Genetic Diseases, Inborn / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genome, Human / genetics*
  • Genomics / methods
  • Genomics / statistics & numerical data
  • Genomics / trends
  • Humans
  • Mutation*
  • Open Reading Frames / genetics
  • Polymorphism, Genetic
  • Regulatory Sequences, Nucleic Acid / genetics